Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00635878" target="_blank" >RIV/61388963:_____/25:00635878 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/25:10498296

Result on the web

<a href="https://doi.org/10.1007/s10238-025-01713-z" target="_blank" >https://doi.org/10.1007/s10238-025-01713-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10238-025-01713-z" target="_blank" >10.1007/s10238-025-01713-z</a>

Result language

angličtina

Original language name

Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma

Original language description

Genomic alterations and enormous monoclonal immunoglobulin production cause multiple myeloma to heavily depend on proteostasis mechanisms, including protein folding and degradation. These findings support the use of proteasome inhibitors for treating multiple myeloma and mantle cell lymphoma. Myeloma treatment has evolved, especially with the availability of new drugs, such as proteasome inhibitors, into therapeutic strategies for both frontline and relapsed/refractory disease settings. However, proteasome inhibitors are generally not effective enough to cure most patients. Natural resistance and eventual acquired resistance led to relapsed/refractory disease and poor prognosis. Advances in the understanding of cellular proteostasis and the development of innovative drugs that also target other proteostasis network components offer opportunities to exploit the intrinsic vulnerability of myeloma cells. This review outlines recent findings on the molecular mechanisms regulating cellular proteostasis pathways, as well as resistance, sensitivity, and escape strategies developed against proteasome inhibitors and provides a rationale and examples for novel combinations of proteasome inhibitors with FDA-approved drugs and investigational drugs targeting the NRF1 (NFE2L1)-mediated proteasome bounce-back response, redox homeostasis, heat shock response, unfolding protein response, autophagy, and VCP/p97 to increase proteotoxic stress, which can improve the efficacy of antimyeloma therapy based on proteasome inhibitors.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

CLINICAL AND EXPERIMENTAL MEDICINE

ISSN

1591-8890

e-ISSN

1591-9528

Volume of the periodical

25

Issue of the periodical within the volume

1

Country of publishing house

IT - ITALY

Number of pages

21

Pages from-to

176

UT code for WoS article

001495322000002

EID of the result in the Scopus database

2-s2.0-105006451879